TY - JOUR
T1 - P53 status influences regulation of HSPs and ribosomal proteins by PDTC and radiation
AU - Thompson, John S.
AU - Asmis, Reto
AU - Glass, Judith
AU - Liu, Hua
AU - Wilson, Colin
AU - Nelson, Brandy
AU - Brown, Stephen A.
AU - Stromberg, Arnold J.
PY - 2006/5/5
Y1 - 2006/5/5
N2 - Pyrrolidine dithiocarbamate (PDTC) is a thiol-containing compound that can act under varying conditions as an anti-oxidant or pro-oxidant. Utilizing microarrays, we determined the effect of PDTC +/- ionizing radiation (IR) on the expression of heat shock protein (HSP) genes in isolated B6/129 wild-type (WT) and p53-/- spleen cells. Extremely significant microarrays demonstrated that PDTC, but not IR, markedly up-regulated the expression of the majority of detectable HSP genes in WT and many to a significantly greater degree in p53-/- deficient cells. Determination of the glutathione/glutathione disulfide ratio indicated that PDTC was acting as a pro-oxidant under these conditions. From these data we conclude that the clinical use of "antioxidants" with radiotherapy or chemotherapy must be very carefully based on knowledge of the p53 status of their intended normal and tumor target cells.
AB - Pyrrolidine dithiocarbamate (PDTC) is a thiol-containing compound that can act under varying conditions as an anti-oxidant or pro-oxidant. Utilizing microarrays, we determined the effect of PDTC +/- ionizing radiation (IR) on the expression of heat shock protein (HSP) genes in isolated B6/129 wild-type (WT) and p53-/- spleen cells. Extremely significant microarrays demonstrated that PDTC, but not IR, markedly up-regulated the expression of the majority of detectable HSP genes in WT and many to a significantly greater degree in p53-/- deficient cells. Determination of the glutathione/glutathione disulfide ratio indicated that PDTC was acting as a pro-oxidant under these conditions. From these data we conclude that the clinical use of "antioxidants" with radiotherapy or chemotherapy must be very carefully based on knowledge of the p53 status of their intended normal and tumor target cells.
KW - Heat shock proteins
KW - Ionizing radiation
KW - Microarray
KW - p53
KW - Pyrrolidine dithiocarbamate
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UR - http://www.scopus.com/inward/citedby.url?scp=33645111444&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2006.02.159
DO - 10.1016/j.bbrc.2006.02.159
M3 - Article
C2 - 16546138
AN - SCOPUS:33645111444
SN - 0006-291X
VL - 343
SP - 435
EP - 442
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 2
ER -